Conventional white light imaging-assisted transurethral resection of bladder tumour (TURBT) versus IMAGE1S-assisted TURBT in non-muscle-invasive bladder cancer patients: trial protocol and 18 months results.

PURPOSE: White light (WL) is the traditional imaging modality for transurethral resection of bladder tumour (TURBT). IMAGE1S is a likely addition. We compare 18-mo recurrence rates following TURBT using IMAGE1S versus WL guidance. METHODS: Twelve international centers conducted a single-blinded randomized controlled trial. Patients with primary and recurrent non-muscle-invasive bladder cancer (NMIBC) were randomly assigned 1:1 to TURBT guided by IMAGE1S or WL. Eighteen-month recurrence rates and subanalysis for primary/recurrent and risk groups were planned and compared by chi-square tests and survival analyses. RESULTS: 689 patients were randomized for WL-assisted (n = 354) or IMAGE1S-assisted (n = 335) TURBT. Of these, 64.7% had a primary tumor, 35.3% a recurrent tumor, and 4.8%, 69.2% and 26.0% a low-, intermediate-, and high-risk tumor, respectively. Overall, 60 and 65 patients, respectively, completed 18-mo follow-up, with recurrence rates of 31.0% and 25.4%, respectively (p = 0.199). In patients with primary, low-/intermediate-risk tumors, recurrence rates at 18-mo were significantly higher in the WL group compared with the IMAGE1S group (31.9% and 22.3%, respectively: p 0.035). Frequency and severity of adverse events were comparable in both treatment groups. Immediate and adjuvant intravesical instillation therapy did not differ between the groups. Potential limitations included lack of uniformity of surgical resection, central pathology review, and missing data. CONCLUSION: There was not difference in the overall recurrence rates between IMAGE1S and WL assistance 18-mo after TURBT in patients with NMIBC. However, IMAGE1S-assisted TURBT considerably reduced the likelihood of disease recurrence in primary, low/intermediate risk patients. REGISTRATION: ClinicalTrials.gov Identifier NCT02252549 (30-09-2014).

Salvage robotic-assisted radical prostatectomy: oncologic and functional outcomes from two high-volume institutions.

INTRODUCTION: While no consensus on the optimal salvage treatment exists, only 3% of these patients will get salvage radical prostatectomies due to the assumed technical challenges of this procedure. OBJECTIVES: Our goal is to analyze the perioperative, oncologic and functional outcomes of patients undergoing salvage robotic-assisted radical prostatectomy (sRARP) after primary treatment failure. MATERIALS AND METHODS: Data were prospectively collected and retrospectively reviewed from a combined database of more than 14,800 patients who had undergone RARP. We identified 96 patients who underwent sRARP after RT or ablative techniques. Primary cancer characteristics, surgical data, pathology results, perioperative complications, oncologic and functional outcomes were analyzed. RESULTS: Sixty-eight patients (70.8%) received some source of RT as a primary treatment. The remaining 28 patients: 18 (18.75%) received cryotherapy, seven (7.92%) HIFU, one electroporation, one microwave and one Tookad. complication was seen in 25 (26%) patients (21 minor and 4 major complications). Anastomotic leak was the most common complication, found in 14 (14.6%) of the cases. No rectal injuries occurred. Fourteen (15%) patients had a biochemical failure after a median follow-up of 14 (IQR 5-24) months. Fifty-five (57.3%) of them self-reported to be pad-free at 12 months. Seventeen (55%) of 31 pre-operative potent patients (SHIM score > 21), were potent with or without the use of PDE5i at 12 months. CONCLUSIONS: sRARP is a feasible alternative for PCa recurrence. Technically the procedure is challenging and should be performed by experienced PCa surgeons. Major complications are uncommon. Continence and potency recovery is possible, but at lower rates than for non-salvage patients.

Comparative Analysis of Partial Gland Ablation and Radical Prostatectomy to Treat Low and Intermediate Risk Prostate Cancer: Oncologic and Functional Outcomes.

PURPOSE: We analyzed the oncologic and functional outcomes of partial gland ablation compared with robot-assisted radical prostatectomy in patients with low and intermediate risk prostate cancer. MATERIALS AND METHODS: A total of 1,883 patients underwent robot-assisted radical prostatectomy and 373 underwent partial gland ablation from July 2009 to September 2015. We selected 1,458 of these participants for analysis, including 1,222 and 236 treated with robot-assisted radical prostatectomy and partial gland ablation, respectively. Patients had a Gleason score of 3 + 3 or 3 + 4, clinical stage T2b or less, prostate specific antigen 15 ng/dl or less, unilateral disease and life expectancy greater than 10 years. Propensity score matching analysis (1:2) was applied in the overall robot-assisted radical prostatectomy sample, which selected 472 patients for comparison. For partial gland ablation 188 men underwent high intensity focused ultrasound and 48 underwent cryotherapy. Oncologic outcomes were analyzed in terms of the need for salvage treatment. Partial gland ablation failure was defined as any positive control biopsy after treatment. Functional outcomes were assessed by validated questionnaires. RESULTS: Matching was successful across the 2 groups, although men treated with partial gland ablation were older (p <0.001). Mean followup in the partial gland ablation group was 38.44 months. Partial gland ablation failure was observed in 68 men (28.8%), including 53 (28.1%) treated with high intensity focused ultrasound and 15 (31.2%) treated with cryotherapy. Partial gland ablation was associated with a higher risk of salvage treatment (HR 6.06, p <0.001). Complications were comparable between the groups (p = 0.06). Robot-assisted radical prostatectomy was associated with less continence recovery and a lower potency rate 3, 6 and 12 months after surgery (p <0.001). CONCLUSIONS: In select patients with organ confined prostate cancer partial gland ablation offered good oncologic control with fewer adverse effects that required additional treatments. Potency and continence appeared to be better preserved after partial gland ablation.

[Opportunities and risks of 5α reductase inhibitors in the medical management of Active surveillance for localized prostate cancer]. / Oportunidad y riesgos de los inhibidores de la 5α reductasa en el manejo medico de la Vigilancia Ativa en cancer de prostata localizado.

Active surveillance (AS) as a therapeutic option is already integrated as a primary treatment strategy in low risk localized prostate cancer (PCa). There is a recent interest for the search of therapeutic interventions that result in a delay in the progression of such indolent cancers. The evaluation of the possible implication of 5 ARI drugs in the reduction of the risk of progression of PCa was enacted by the results of the clinical trials PCPT (Prostate Cancer Prevention Trial) and REDUCE (Reduction by Dutasteride of Prostate Cancer Events study). The results of the REDEEM clinical trial (Reduction by Dutasteride of clinical progression events in expectant management trial) revealed a delay in PCa progression favoring Dutasteride in comparison with placebo, being advanced age and PSA Density independent predictive factors for pathologic progression. Evidences regarding the influence of 5 ARIs in the evolution of AS patients come from few studies with limited follow up. Thus, the conclusions probably are far from being consiidered as definitive.

EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent.

BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines provide recommendations for the management of clinically localised prostate cancer (PCa). This paper aims to present a summary of the 2024 version of the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on the screening, diagnosis, and treatment of clinically localised PCa. METHODS: The panel performed a literature review of all new data published in English, covering the time frame between May 2020 and 2023. The guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence. KEY FINDINGS AND LIMITATIONS: A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for selected favourable intermediate-risk patients with International Society of Urological Pathology grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term intensified hormonal treatment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa guidelines reflect the multidisciplinary nature of PCa management. PATIENT SUMMARY: This article is the summary of the guidelines for "curable" prostate cancer. Prostate cancer is "found" through a multistep risk-based screening process. The objective is to find as many men as possible with a curable cancer. Prostate cancer is curable if it resides in the prostate; it is then classified into low-, intermediary-, and high-risk localised and locally advanced prostate cancer. These risk classes are the basis of the treatments. Low-risk prostate cancer is treated with "active surveillance", a treatment with excellent prognosis. For low-intermediary-risk active surveillance should also be discussed as an option. In other cases, active treatments, surgery, or radiation treatment should be discussed along with the potential side effects to allow shared decision-making.

EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer. Part II-2024 Update: Treatment of Relapsing and Metastatic Prostate Cancer.

BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (PCa) have been updated. Here we provide a summary of the 2024 guidelines. METHODS: The panel performed a literature review of new data, covering the time frame between 2020 and 2023. The guidelines were updated and a strength rating for each recommendation was added on the basis of a systematic review of the evidence. KEY FINDINGS AND LIMITATIONS: Risk stratification for relapsing PCa after primary therapy may guide salvage therapy decisions. New treatment options, such as androgen receptor-targeted agents (ARTAs), ARTA + chemotherapy combinations, PARP inhibitors and their combinations, and prostate-specific membrane antigen-based therapy have become available for men with metastatic PCa. CONCLUSIONS AND CLINICAL IMPLICATIONS: Evidence for relapsing, metastatic, and castration-resistant PCa is evolving rapidly. These guidelines reflect the multidisciplinary nature of PCa management. The full version is available online (http://uroweb.org/guideline/ prostate-cancer/). PATIENT SUMMARY: This article summarises the 2024 guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are based on evidence and guide doctors in discussing treatment decisions with their patients. The guidelines are updated every year.

[Patient with testosterone deficit syndrome after radical prostatectomy]. / Paciente con síndrome de déficit de testosterona tras prostatectomía radical.

Testosterone Deficiency Syndrome is associated with age. Recent studies advocate for the safety of hormonal treatment with testosterone in patients with history of Prostate Cancer (PC) ,once disease-free survival is confirmed. A total of five publications describe 110 patients treated with testosterone replacement therapy, having a history of PC, who had undergone radical prostatectomy (RP). Only one patient had biochemical recurrence during replacement therapy. Testosterone replacement therapy must be indicated in selected patients with history of low risk localized prostate cancer treated satisfactorily who are symptomatic and have good oncological control. The testosterone levels to achieve should be the minimum effective to obtain a symptomatic response. Adequate information on the benefits and potential risks must be understood and accepted by the patient.

[Patient with testosterone deficit syndrome and erectile dysfunction non-responder to PDE-5 inhibitors]. / Paciente con sdt y ed no respondedor a inhibidores de la 5PDE.

Androgens play an essential role in the corporo-venous occlusive mechanism that provokes erection. Accordingly to various studies based on animal models,testosterone deficit syndrome causes an endothelial disorder in the corpora cavernosa with diminished secretion of NO, alteration of penile smooth muscle and tunica albuginea structure, and increase of the number of adipocytes within the erectile tissue, which favors fibrosis and impairs erection. All these alterations are reversible with the exogenous administration of androgens. There are not enough studies to get definitive conclusions about androgen supply improving erectile dysfunction in patients with hypogonadism. Studies have been published in which seems that exogenous testosterone could be useful in the treatment of this type of patients. Nevertheless,in most published randomized double blind studies comparing with placebo, testosterone supply does not provide greater benefit on erectile dysfunction than PDE-5 Inhibitors exclusively. All studies coincide in the need to optimize the treatment with PDE-5 Inhibitors since they do have proven to be effective for the treatment of erectile dysfunction in patients with testosterone deficit syndrome.

Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.

CONTEXT: The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed. OBJECTIVE: To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent. EVIDENCE ACQUISITION: A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021. EVIDENCE SYNTHESIS: We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy. CONCLUSIONS: Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers. PATIENT SUMMARY: We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact.

A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer.

CONTEXT: The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain. OBJECTIVE: To perform a systematic review to determine the benefits and harms of EBRT-BT. EVIDENCE ACQUISITION: Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs). EVIDENCE SYNTHESIS: Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p < 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs. CONCLUSIONS: EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control. PATIENT SUMMARY: We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.

[Usefulness of the g8 questionnaire in predicting frailty in elderly patients with metastatic or castration-resistant prostate cancer.] / Utilidad de cuestionario G8 en la predicción de fragilidad en pacientes ancianos con cáncer de próstata metastásico o resistente a castración.

OBJECTIVE: to assess the capacityof the G8 questionnaire for the detection of frailty inpatients over 75 years of age with metastatic or castrationresistant prostate cancer and the relationshipof the results of this questionnaire with clinical variables,laboratory data, quality of life, functional statusand comorbidity. MATERIAL AND METHODS: Patients over the ageof 75 with metastatic or castration-resistant prostatecancer were evaluated using the G8 questionnaire.Those with a G8 15 were subjected to comprehensivegeriatric assessment in order to evaluate the abilityof this questionnaire to predict frailty. We studiedthe relationship between G8 score and functionalstatus (ECOG), comorbidity (Charlson index), qualityof life (FACT-P and EQ5D 3L questionnaires), diseasecharacteristics and common analytical variables. RESULTS: 64 patients were included in the study,of whom 26 scored 15 in the G8 questionnaireand were referred to geriatrics. 89% (23/26) of thepatients with a G8 score pre-fragile and 7 fragile) and only 11% (3/26) wereconsidered robust. The multivariate model showsthat the Charlson index and the EQ5D 3L score areindependent predictors of frailty. The Charlson index(OR=1.68, p=0.022) increases the probability thatthe patient has a G8 score the EQ5D-3L score (OR-0.64, p-0.021) decreases thatprobability. Both quantitative variables were recodedinto binary variables from the most predictivepoint obtained from the ROC curves and included ina model: patients with Charlson index ≥4 (OR=3.17,p=0.047) and those with EQ5D- 3L score (OR=3.35, p=0.037) increased the likelihood of obtaininga G8 scoreconditions (neither Charlson ≥4 nor EQ5D-3L score 15. However, the presence of the two conditions increasesthe probability to 71.5%. CONCLUSIONS: The score obtained in the G8questionnaire is a good predictor of frailty in elderlypatients with advanced prostate cancer. Comorbidity,as measured by Charlson's index, and quality of life,as measured by the EQ5D-3L questionnaire, are independentpredictors of frailty (score on the G8 questionnairebelow 15).

OBJETIVO: Valorar la capacidad delcuestionario G8 para la detección de fragilidad enpacientes mayores de 75 años con cáncer de próstatametastásico o resistente a castración y la relación de losresultados de este cuestionario con variables clínicas,datos de laboratorio, calidad de vida, estado funcionaly comorbilidad.MATERIAL Y MÉTODOS: Se evaluó a pacientes ≥ 75años con cáncer de próstata metastásico o resistente acastración mediante el cuestionario G8. Aquellos conuna puntuación menor de 15 fueron sometidos a valoracióngeriátrica integral. Se evaluó la capacidad dedicho cuestionario para predecir fragilidad y se relacionaronlos hallazgos con el estado funcional (ECOG),comorbilidad (índice de Charlson), calidad de vida(cuestionarios FACT-P y EQ5D 3L), características de laenfermedad y variables analíticas habituales. RESULTADOS: Se incluyeron en el estudio 64 pacientes,de los cuales 26 obtuvieron una puntuación inferior a 15 en el cuestionario G8 y fueron remitidosal servicio de geriatría. El 89% (23/26) de los pacientescon una puntuación en el G8 por debajo de 15 presentabandatos de fragilidad (11 prefrágiles y 7 frágiles) ysolo el 11% (3/26) fueron considerados robustos. Elmodelo multivariado muestra, que de manera independiente,el índice de Charlson (OR=1,68, p=0,022)aumenta la probabilidad de que el paciente tenga unapuntuación en el cuestionario G8 por debajo de 15 y lapuntuación en el EQ5D-3L (OR=0,64, p=0,021) disminuyadicha probabilidad. Ambas variables cuantitativasse recodificaron en variables de tipo binario a partir delpunto más predictivo obtenido de las curvas ROC y seincluyeron en un modelo en el cual se objetivó, que pacientescon índice de Charlson ≥4 (OR= 3,17, p=0,047)y aquellos con puntuación en el cuestionario EQ5D-3Lde presentar una puntuación en el cuestionario G8Los pacientes que no presentan ninguna de estas condiciones(ni Charlson ≥4 ni EQ5D-3L score un 19% de probabilidad de presentar una puntuaciónen el cuestionario G8 condiciones aumenta la probabilidad hasta el 71,5%. CONCLUSIONES: La puntuación obtenida en elcuestionario G8 es un buen predictor de fragilidad enpacientes con cáncer de próstata avanzado con edad≥ 75 años. La comorbilidad, medida por el índice deCharlson, y la calidad de vida, medida por el cuestionarioEQ5D-3L, son predictores independientes de fragilidad,entendida como la obtención de una puntuaciónen el cuestionario G8 por debajo de 15.

Management of Patients with Metastatic Bladder Cancer in the Real-World Setting from the Multidisciplinary Team: Current Opinion of the SOGUG Multidisciplinary Working Group.

Based on the discussion of current state of research of relevant topics of metastatic bladder cancer (mBC) among a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group, a set of recommendations were proposed to overcome the challenges posed by the management of mBC in clinical practice. First-line options in unfit patients for cisplatin are chemotherapy with carboplatin and immunotherapy in PD-L1 positive patients. FDG-PET/CT may be a useful imaging technique in the initial staging or re-staging. In patients with oligometastatic disease, it is important to consider not only the number of metastatic lesions, but also the tumor biology and the clinical course. The combination of stereotactic body radiotherapy and immunotherapy with anti-PD-L1 monoclonal antibodies is under investigation and could improve the results of systemic treatment in patient with oligometastatic disease. Rescue treatment with curative intent could be considered in patients with oligometastatic disease after complete response on FDG-PET/CT. Metastatic disease should be evaluated using the same imaging modality over the course of the disease from diagnosis until rescue treatment. For improving the outcome of patients with mBC, the involvement of a dedicated multidisciplinary team, including urologists, pathologists, oncologists, radiologists and other specialists is of outmost importance in the daily care of these patients.

Combination therapy with topical alprostadil and phosphodiesterase-5 inhibitors after failure of oral therapy in patients with erectile dysfunction: a prospective, two-arm, open-label, non-randomized study.

Phosphodiesterase type 5 inhibitors (PDE5Is) are the first-line therapeutic option for erectile dysfunction (ED), while second-line therapy includes the alprostadil. Due to the different pharmacodynamic mechanism of PDE5Is and alprostadil, a synergistic action is conceivable when they are administered in combination. The aim of present study was to evaluate the efficacy and safety of combination therapy with PDE5I and topical alprostadil in patients with ED non-responders to PDE5I alone. We designed a prospective, two-arm, open-label, non-randomized study. Patients over 18 years old, with a stable sexual relationship for at least 6 months, and ED non-responders to PDE5I monotherapy were included in the study. At baseline the variables assessed were 5-item version of the International Index of Erectile Function (IIEF-5), and Sexual Encounter Profile Questions 2 and 3 (SEP-2 and SEP-3). In addition, all subjects underwent penile dynamic duplex ultrasonography. All patients were assigned to the monotherapy group (Group A) or combination therapy group (Group B) based on their preference. Topical alprostadil 300 µg/100 mg (Virirec®) was the treatment assigned to Group A, while the combination therapy with the last PDE5I taken (at the maximum recommended dose) plus topical alprostadil 300 µg/100 mg (Virirec®) was assigned to Group B. After 3 months from assignment to groups were evaluated IIEF-5, SEP-2 and SEP-3 regarding the last sexual intercourse, and Global Assessment Questionnaire-Questions 1 and 2 (GAQ-1 and GAQ-2). All adverse events (AEs) that occurred during the study period were recorded. A total of 170 patients were included in the study (72 in Group A and 98 in Group B). Fifty-two patients were previously treated with sildenafil 100 mg (30.6%), 6 with vardenafil 20 mg (3.5%), 56 with tadalafil 20 mg (32.9%), and 56 with avanafil 200 mg (32.9%). No significant differences among the study groups were found at baseline (p > 0.05). The mean IIEF-5 score increased significantly in Group B after treatment compared to baseline (12.4 ± 3.4 vs. 17.1 ± 4.5; p < 0.001), conversely patients in Group A showed no significant increase (12.2 ± 2.5 vs. 12.7 ± 3.1; p = 0.148). The number of affirmative responses to SEP-2 was significantly higher after treatment compared to baseline only in Group B (57 vs. 78; p < 0.001). The number of affirmative responses to SEP-3 was significantly higher after treatment compared to baseline in both groups (p < 0.001). The number of affirmative responses to GAQ-Q1 and GAQ-Q2 was significantly higher in Group B compared to Group A (p < 0.001). A total of 59 (34.7%) patients experienced AEs. They were mild, self-limited, and did not cause discontinuation of treatment. No episode of priapism was recorded. No statistically significant difference was recorded between the AEs of the two groups, except for facial flushing that was reported only in Group B (p = 0.021). The combination therapy with topical alprostadil and PDE5I seems to be more effective than topical alprostadil alone without worsening the safety of the treatment.

New frontiers in focal therapy for prostate cancer: Prostate-specific membrane antigen positron emission tomography/magnetic resonance imaging.

Imaging has a central role in the context of focal therapy (FT) for prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) positron emission tomography/magnetic resonance imaging (PET/MRI) is a novel imaging modality that combines the morpho-functional information of MRI with the molecular characterization of PET. Some papers reported the potential advantages of PSMA PET/MRI in different clinical scenarios. Limited evidence on PSMA PET/MRI is available in the setting of FT. PSMA PET/MRI can be an effective imaging modality for detecting primary PCa and seems to provide accurate local staging of primary PCa. PSMA PET/MRI also shows high performance for restaging and detecting tumor recurrence. The higher soft-tissue contrast and the reduction of ionizing radiation are the main advantages reported in the literature compared to PET/computed tomography. PSMA PET/MRI could represent a turning point in the management of patients with PCa in the context of FT. Further studies are needed to confirm its applications in this specific clinical setting.

European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines.

CONTEXT: This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). OBJECTIVE: To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. EVIDENCE ACQUISITION: A broad and comprehensive scoping exercise covering all areas of the MMIBC guideline has been performed annually since its 2017 publication (based on the 2016 guideline). Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. A level of evidence and a grade of recommendation were assigned. Additionally, the results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted. EVIDENCE SYNTHESIS: Variant histologies are increasingly reported in invasive BC and are relevant for treatment and prognosis. Staging is preferably done with (enhanced) computerised tomography scanning. Treatment decisions are still largely based on clinical factors. Radical cystectomy (RC) with lymph node dissection remains the recommended treatment in highest-risk non-muscle-invasive and muscle-invasive nonmetastatic BC, preceded by cisplatin-based neoadjuvant chemotherapy (NAC) for invasive tumours in "fit" patients. Selected men and women benefit from sexuality sparing RC, although this is not recommended as standard therapy. Open and robotic RC show comparable outcomes, provided the procedure is performed in experienced centres. For open RC 10, the minimum selected case load is 10 procedures per year. If bladder preservation is considered, chemoradiation is an alternative in well-selected patients without carcinoma in situ and after maximal resection. Adjuvant chemotherapy should be considered if no NAC was given. Perioperative immunotherapy can be offered in clinical trial setting. For fit metastatic patients, cisplatin-based chemotherapy remains the first choice. In cisplatin-ineligible patients, immunotherapy in Programmed Death Ligand 1 (PD-L1)-positive patients or carboplatin in PD-L1-negative patients is recommended. For second-line treatment in metastatic disease, pembrolizumab is recommended. Postchemotherapy surgery may prolong survival in responders. Quality of life should be monitored in all phases of treatment and follow-up. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/. CONCLUSIONS: This summary of the 2020 EAU MMIBC guideline provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. PATIENT SUMMARY: The European Association of Urology Muscle-invasive and Metastatic Bladder Cancer (MMIBC) Panel has released an updated version of their guideline, which contains information on histology, staging, prognostic factors, and treatment of MMIBC. The recommendations are based on the current literature (until the end of 2019), with emphasis on high-level data from randomised clinical trials and meta-analyses and on the findings of an international consensus meeting. Surgical removal of the bladder and bladder preservation are discussed, as well as the use of chemotherapy and immunotherapy in localised and metastatic disease.

Invasive management of renal cell carcinoma in von Hippel-Lindau disease.

INTRODUCTION: Patients affected by von Hippel-Lindau (VHL) disease experience an increased risk for bilateral, synchronous, and metachronous renal cell carcinoma (RCC). Oncologic and functional outcomes are the main goals in the management of renal masses. We present our protocol for patients with VHL disease-associated RCC alongside functional and oncologic results observed in our series. MATERIAL AND METHODS: We performed a retrospective analysis of our clinical database of patients with VHL disease-associated RCC referred to our department between June 2005 and December 2017. We offer surveillance for lesions <2 cm and active management with radiofrequency ablation (RFA) for lesions 2-3 cm, and nephron-sparing surgery (NSS), RFA or embolization techniques for lesions >3 cm or growth rate >1 cm/year. RESULTS: Our series comprises 14 patients, of whom 13 had undergone at least one invasive procedure for RCC, mean age at first intervention was 27 years (range 18-60). Overall, 30 interventions were performed in 21 kidneys: four radical nephrectomies, 13 RFAs, 12 NSSs, and one embolization. During follow-up (median time: 41 months, range: 6-149), eight patients (57%) presented with new lesions that required treatment, with a mean time between treatments of 32 ±18.5 months. No metastatic progression or need for dialysis was recorded; the success rate for RFA was 85%. CONCLUSIONS: Management of VHL kidney disease by NSS is the standard of care with a cut-off at 3 cm, ablative procedures should be offered to lesions ranging 2-3 cm in size. Follow-up should be done strictly in referral centers that can provide all treatment options to renal function and control oncologic progression.

Renal cell carcinoma and COVID-19 pandemia: Management strategies adapted to current practice. / Pandemia Covid-19 y cáncer renal: implicaciones y adaptación para un manejo óptimo de la enfermedad.

The COVID-19 pandemic caused by SARS-CoV-2 virus has caused an important health impact that has affected renal cell carcinoma management, among other urology areas. The high cancellation rate of surgeries, including those related to renal cancer, will cause an inevitable healthcare overload and probably a potential negative impact on its oncological outcomes, especially in locally advanced and metastatic renal cancer. Kidney cancer scenarios are quite different depending on their stage, distinguishing mainly between low priority of localized disease or high priority of locally advanced and metastatic under active treatment. The unknown pandemic duration and possibly fluctuating prevalence of the virus are likely to force an adaptation in the management of renal cell carcinoma among urology and oncology departments, ideally individualized ona case-by-case basis within multidisciplinary units. To this end, we present algorithms and tables regarding renal cell carcinoma management adapted to the COVID-19 period and stratified according to oncological stage, which might be useful for specialists dedicated to this uro-oncology area.

La pandemia COVID-19 causada por el virus SARS-CoV-2 ha provocado un importante impacto sanitario que ha afectado, entre otras áreas de la urología, al manejo del cáncer renal, tanto en su ámbito diagnóstico como de tratamiento. La elevada suspensión de intervenciones quirúrgicas, incluidas aquellas destinadas al tratamiento de esta patología, ocasionará una inevitable sobrecarga asistencial y quizá un potencial efecto deletéreo sobre sus resultados oncológicos, en especial en el cáncer renal localmente avanzado y en el metastásico. Los escenarios clínicos del carcinoma de células renales son bien distintos en función de su estadiaje, distinguiendo principalmente entre la baja prioridad de la enfermedad localizada o la alta prioridad del localmente avanzado y el metastásico en tratamiento activo. La duraciónin determinada y prevalencia posiblemente oscilante de la pandemia previsiblemente obligue a adaptar el manejo del cáncer renal en los servicios de urología y oncología, debiendo ser idealmente invidualizados según cada caso en el seno de unidades multidisciplinares. Para ello, se presentan algoritmos y tablas de manejo del cáncer renal adaptadas al periodo COVID-19 y estratificados según el estadio de la enfermedad, que puedan ser de utilidad para los especialistas dedicados a esta área de la uro-oncología.

Genetic testing for the clinician in prostate cancer.

INTRODUCTION: Prostate cancer (PCa) is one of the most common cancers worldwide and a leading cause of cancer-related mortality. Although the diagnosis and treatment of prostate cancer has improved substantially in recent years, new molecular biomarkers are needed to further prolong survival and improve the quality of life in these patients. AREAS COVERED: This review analyzes the current evidence for prognostic and predictive molecular biomarkers that can be applied across different clinical scenarios, ranging from localized disease to metastatic castration-resistant PCa, with a particular emphasis on the biomarkers likely to become available in routine clinical practice in the near future. EXPERT OPINION: There is a growing need for molecular testing to identify the most indolent types of prostate cancer to help optimize treatment strategies and spare treatment in these patients when possible. Current trends in the treatment of prostate cancer underscore the unmet clinical need for biomarkers to improve decision-making in a challenging clinical setting.

Rates and Predictors of Perioperative Complications in Cytoreductive Nephrectomy: Analysis of the Registry for Metastatic Renal Cell Carcinoma.

BACKGROUND: Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients. OBJECTIVE: We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes. DESIGN, SETTING, AND PARTICIPANTS: Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates. RESULTS AND LIMITATIONS: Intraoperative complications were observed in 69 patients (10.9%). Thrombectomy (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08-1.75, p = 0.009) and adjacent organ removal (OR 2.7, 95% CI 1.38-5.30) were significant predictors of intraoperative complications at multivariable analysis. Two hundred seventeen patients (29.5%) encountered AGCs, while 45 (6.1%) encountered an HGC, of whom 10 (1.4%) died. Twenty-four (3.3%) patients had multiple postoperative complications. Estimated blood loss (EBL; OR 1.49, 95% CI 1.08-2.05, p = 0.01) was a significant predictor of AGCs at multivariable analysis. CN case load (OR 0.13, 95% CI 0.03-0.59, p = 0.009) and EBL (OR 2.93, 95% CI 1.20-7.15, p = 0.02) were significant predictors solely for HGCs at multivariable analysis. Forty-one patients (11.5%) were readmitted within 30 d of surgery. No significant predictors were identified. Results were confirmed in a subanalysis focusing solely on patients treated in the contemporary targeted therapy era. CONCLUSIONS: Morbidity associated with CN is not negligible. Predictors of high-grade postoperative morbidity are predominantly indicators of complex surgery. EBL is a strong predictor of postoperative complications. CN case load correlates with lower high-grade morbidity and highlights the benefit of centralization of complex surgery. However, risks and benefits should be balanced when considering CN in mRCC patients. PATIENT SUMMARY: We studied patients with metastatic renal cancer to evaluate the outcomes associated with the surgical removal of the primary kidney tumor. We found that this procedure is often complex and adverse events are not uncommon. High intraoperative blood loss and a small number of cases performed at the treating center are associated with a higher rate of postoperative complications.

European Association of Urology Guidelines on Primary Urethral Carcinoma-2020 Update.

CONTEXT: Primary urethral carcinoma (PUC) is a rare cancer accounting for <1% of all genitourinary malignancies. OBJECTIVE: To provide updated practical recommendations for the diagnosis and management of PUC. EVIDENCE ACQUISITION: A systematic search interrogating Ovid (Medline), EMBASE, and the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews was performed. EVIDENCE SYNTHESIS: Urothelial carcinoma of the urethra is the predominant histological type of PUC (54-65%), followed by squamous cell carcinoma (16-22%) and adenocarcinoma (10-16%). Diagnosis of PUC depends on urethrocystoscopy with biopsy and urinary cytology. Pathological staging and grading are based on the tumour, node, metastasis (TNM) classification and the 2016 World Health Organization grading systems. Local tumour extent and regional lymph nodes are assessed by magnetic resonance imaging, and the presence of distant metastases is assessed by computed tomography of the thorax/abdomen and pelvis. For all patients with localised distal tumours (≤T2N0M0), partial urethrectomy or urethra-sparing surgery is a valid treatment option, provided that negative intraoperative surgical margins can be achieved. Prostatic Ta-Tis-T1 PUC can be treated with repeat transurethral resection of the prostate and bacillus Calmette-Guérin. In prostatic or proximal ≥ T2N0 disease, neoadjuvant cisplatin-based chemotherapy should be considered prior to radical surgery. All patients with locally advanced disease (≥T3N0-2M0) should be discussed within a multidisciplinary team. In men with locally advanced squamous cell carcinoma, curative radiotherapy combined with radiosensitising chemotherapy can be offered for definitive treatment and genital preservation. In patients with local urethral recurrence, salvage surgery or radiotherapy can be offered. For patients with distant metastatic disease, systemic therapy based on tumour characteristics can be evaluated. CONCLUSIONS: These updated European Association of Urology guidelines provide up-to-date guidance for the contemporary diagnosis and management of patients with suspected PUC. PATIENT SUMMARY: Primary urethral carcinoma (PUC) is a very rare, but aggressive disease. These updated European Association of Urology guidelines provide evidence-based guidance for clinicians treating patients with PUC.